Evaluation of digestive tolerance of a soluble corn fibre

Background: To assess consumers’ acceptance of a new fibre, it is essential to evaluate its digestive tolerance after ingestion. We aimed to determine the tolerance of increasing dosages of Promitor? Soluble Gluco Fibre (SGF; Tate&Lyle, Hoffman Estates, IL, USA) up to 70 g fibre per day using a validated gastrointestinal composite score. Methods: A composite score of gastrointestinal tolerance integrating gastrointestinal symptoms, stool frequency and consistency was applied. To statistically validate this composite score, the gastrointestinal tolerance of inulin (10 g versus 20 g containing, respectively, 9 g versus 18 g of fibre) was assessed in 18 healthy volunteers in a randomised double‐blind placebo‐controlled cross‐over study. Second, in a double‐blind placebo‐controlled cross‐over study with 20 healthy volunteers, the gastrointestinal tolerance of SGF in both acute and ‘spread over the day’ conditions of consumption was assessed. Results: By contrast to 10 g, 20 g of inulin demonstrated a significant difference in composite score compared to placebo [P < 0.001, difference = 7.6; 95% confidence interval (CI) = 3.8–11.3]. These values were considered as reference during the second study. In acute conditions, 40 g of SGF fibre was the highest (threshold) dose tested that indicates the digestive tolerance criteria (difference from placebo on the composite score <7.6 and upper limit of the 95% CI <11.3); this is twice the amount tolerated for inulin. In ‘spread over the day’ conditions, 65 g of SGF fibre was the threshold dose (P < 0.001, difference = 6.5; 95% CI = 3.4–9.5). Conclusions: The results of the present study demonstrate that 40 g of SGF fibre, when consumed as a single dose, and 65 g of SGF fibre, when consumed in multiple‐doses, across the day are well‐tolerated by healthy volunteers.     

Subtle CD20 positivity in the bone marrow of a patient who has a mucosa‐associated lymphoid tissue lymphoma should not be regarded as evidence of involvement in the bone marrow

Aims: Bone marrow (BM) biopsies of some mucosa‐associated lymphoid tissue (MALT) lymphoma patients show scattered or small clusters of CD20+ cells without definite lesions (subtle CD20 positivity). The aim of this study was to evaluate the clinical significance of BM involvement and subtle CD20 positivity in 122 patients diagnosed with MALT lymphoma. Methods and results: Patients were divided into three categories: BM involvement [BM(+)], subtle CD20 positivity, and no BM involvement [BM(?)]. Eleven (9%) showed BM involvement, and 17 (14%) showed subtle CD20 positivity. BM(+) patients had significantly worse progression‐free survival (PFS) than BM(?) patients [hazard ratio (HR) 6.25, P = 0.01], but there was no significant difference between subtle CD20 positivity and BM(?) patients. Patients with >30 CD3+ cells among 100 nucleated cells in the areas with increased numbers of CD3+ cells had significantly worse PFS than those with <15 CD3+ cells (HR 5.49, P = 0.02). BM(+) patients with >30 CD3+ cells had worse PFS than those with ≤30 CD3+ cells (P = 0.029), with an extent of BM(+) involvement of >10% positively correlating with >30 CD3+ cells (P = 0.015). Conclusions: Patients with BM(+) MALT lymphoma showed significantly worse PFS than those with subtle CD20 positivity and BM(?) MALT lymphoma, but the PFS of patients with subtle CD20 positivity MALT lymphoma was not significantly different from that of those with BM(?) MALT lymphoma. Increased numbers of BM T cells in MALT lymphoma patients might be suggestive of a worse prognosis.     

A non‐fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient

Post‐transplant infections in allogeneic haematopoietic cell transplant (allo‐HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non‐fatal case of Lichtheimia corymbifera infection in an allo‐HCT recipient.     

A continuous‐flow,high‐throughput,high‐pressure parahydrogen converter for hyperpolarization in a clinical setting

Pure parahydrogen (pH₂) is the prerequisite for optimal pH₂‐based hyperpolarization experiments, promising approaches to access the hidden orders of magnitude of MR signals. pH₂ production on‐site in medical research centers is vital for the proliferation of these technologies in the life sciences. However, previously suggested designs do not meet our requirements for safety or production performance (flow rate, pressure or enrichment). In this article, we present the safety concept, design and installation of a pH₂ converter, operated in a clinical setting. The apparatus produces a continuous flow of four standard liters per minute of ≈98% enriched pH₂ at a pressure maximum of 50 bar. The entire production cycle, including cleaning and cooling to 25 K, takes less than 5 h, only ≈45 min of which are required for actual pH₂ conversion. A fast and simple quantification procedure is described. The lifetimes of pH₂ in a glass vial and aluminum storage cylinder are measured to be T_1C(glass vial) = 822 ± 29 min and T_1C(Al cylinder) = 129 ± 36 days, thus providing sufficiently long storage intervals and allowing the application of pH₂ on demand. A dependence of line width on pH₂ enrichment is observed. As examples, ¹H hyperpolarization of pyridine and ¹³C hyperpolarization of hydroxyethylpropionate are presented. Copyright © 2012 John Wiley & Sons, Ltd.     

Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.     

Blocking glutamate‐mediated signalling inhibits human melanoma growth and migration

Glutamate is an excitatory neurotransmitter that has been shown to regulate the proliferation, migration and survival of neuronal progenitors in the central nervous system through its action on metabotropic and ionotropic glutamate receptors (GluRs). Antagonists of ionotropic GluRs have been shown to cause a rapid and reversible change in melanocyte dendritic morphology, which is associated with the disorganization of actin and tubulin microfilaments in the cytoskeleton. Intracellular expression of microtubule‐associated protein (MAP) 2a affects the assembly, stabilization and bundling of microtubules in melanoma cells; stimulates the development of dendrites; and suppresses melanoma cell migration and invasion. In this study, we investigated the relationship between glutamate‐mediated signalling and microtubules, cell dendritic morphology and melanoma cell motility. We found that metabotropic GluR1 and N‐methyl‐d ‐aspartate receptor antagonists increased dendritic branching and inhibited the motility, migration and proliferation of melanoma cells. We also demonstrated that the invasion and motility of melanoma cells are significantly inhibited by the combination of increased expression of MAP2a and either metabotropic GluR1 or N‐methyl‐d ‐aspartate receptor antagonists. Moreover, the blockade of glutamate receptors inhibited melanoma growth in vivo. Collectively, these results demonstrate the importance of glutamate signalling in human melanoma and suggest that the blockade of glutamate receptors is a promising novel therapy for treating melanoma.     

Does the magnetic anal sphincter device compare favourably with sacral nerve stimulation in the management of faecal incontinence?

Aim The magnetic anal sphincter (MAS) is a recent surgical innovation for severe faecal incontinence (FI). With its place in the treatment algorithm of FI yet to be defined, we report a nonrandomized comparison between MAS and sacral nerve stimulation (SNS) in a single‐centre cohort of patients with FI. Method Data were reviewed from prospective databases. From December 2008 to December 2010, 12 women [median age 65 (42–76) years], having FI for a median of 6.5 years, were implanted with a MAS. Sixteen women, of similar age, preoperative function scores, aetiology and duration of incontinence, and implanted with a permanent SNS pulse generator during the same period, served as a reference group. The duration of hospital stay, complications, change in incontinence and quality of life scores and anal physiology were compared between the two groups. Results The duration of follow up was similar [MAS = 18 (8–30) months vs SNS = 22 (10–28) months; P = 0.318]. Four patients with MAS experienced a 30‐day complication, and the device was removed from one patient in each group. A significant improvement in incontinence (P < 0.001) and quality‐of‐life scores (P < 0.04) occurred in both groups. Mean anal resting pressure increased significantly in patients implanted with a MAS (P = 0.027). Conclusion In this single‐centre nonrandomized cohort of FI patients, MAS was as effective as SNS in improving continence and quality of life, with similar morbidity. These results can now serve as a prelude to a randomized trial comparing the procedures.